Abstract

Background

The p53 transcription factor is located at the core of a complex wiring of signaling
pathways that are critical for the preservation of cellular homeostasis. Only recently
it has become clear that p53 regulates the expression of several long intergenic noncoding
RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs
play in this pathway.

Results

Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells,
Pint promotes cell proliferation and survival by regulating the expression of genes of
the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex
2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation
and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified
Pint human ortholog (PINT), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the
same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly,
PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation
of tumor cells, suggesting a possible role as tumor suppressor.

Conclusions

Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects
p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies
and differences between the murine and human orthologs, identifying a novel tumor
suppressor candidate lincRNA.